+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Abeta immunotherapy: intracerebral sequestration of Abeta by an anti-Abeta monoclonal antibody 266 with high affinity to soluble Abeta



Abeta immunotherapy: intracerebral sequestration of Abeta by an anti-Abeta monoclonal antibody 266 with high affinity to soluble Abeta



Journal of Neuroscience 29(36): 11393-8



Amyloid beta (Abeta) immunotherapy is emerging as a promising disease-modifying therapy for Alzheimer's disease, although the precise mechanisms whereby anti-Abeta antibodies act against amyloid deposition and cognitive deficits remain elusive. To test the "peripheral sink" theory, which postulates that the effects of anti-Abeta antibodies in the systemic circulation are to promote the Abeta efflux from brain to blood, we studied the clearance of (125)I-Abeta(1-40) microinjected into mouse brains after intraperitoneal administration of an anti-Abeta monoclonal antibody 266. (125)I-Abeta(1-40) was rapidly eliminated from brains with a half-life of approximately 30 min in control mice, whereas 266 significantly retarded the elimination of Abeta, presumably due to formation of Abeta-antibody complex in brains. Administration of 266 to APP transgenic mice increased the levels of monomer Abeta species in an antibody-bound form, without affecting that of total Abeta. We propose a novel mechanism of Abeta immunotherapy by the class of anti-Abeta antibodies that preferentially bind soluble Abeta, i.e., intracerebral, rather than peripheral, sequestration of soluble, monomer form of Abeta, thereby preventing the accumulation of multimeric toxic Abeta species in brains.

(PDF emailed within 0-6 h: $19.90)

Accession: 051305129

Download citation: RISBibTeXText

PMID: 19741145

DOI: 10.1523/JNEUROSCI.2021-09.2009


Related references

Peripheral anti-Abeta antibody alters CNS and plasma Abeta clearance and decreases Abeta burden in a mouse model of Alzheimers disease. Society for Neuroscience Abstracts 27(2): 1806, 2001

Human anti-Abeta antibodies block Abeta fibril formation and prevent Abeta-induced neurotoxicity. Neurology 60(5 Supplement 1): A69, March 11, 2003

Abeta IMMUNIZATION IN MONKEYS GENERATES ANTI-Abeta TITERS AND INCREASED PERIPHERAL Abeta LEVELS. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 227 6, 2002

Infusion of intravenous immunoglobulin (IVIg) containing anti-abeta antibodies is associated with a decrease of Abeta in cerebrospinal fluid (CSF) and increase of Abeta in blood from 8 patients with mild Alzheimer's disease (AD). Journal of Allergy and Clinical Immunology 121(2-supp-S1), 2008

An Abeta sequestration approach using non-antibody Abeta binding agents. Current Alzheimer Research 2(2): 265-268, 2005

Protective effects of Abeta-derived tripeptide, Abeta(32-34), on Abeta(1-42)-induced phosphatidylinositol 4-kinase inhibition and neurotoxicity. Neuroscience Letters 419(3): 247-252, 2007

p75NTR regulates Abeta deposition by increasing Abeta production but inhibiting Abeta aggregation with its extracellular domain. Journal of Neuroscience 31(6): 2292-2304, 2011

Stabilities and conformations of Alzheimer's beta -amyloid peptide oligomers (Abeta 16-22, Abeta 16-35, and Abeta 10-35): Sequence effects. Proceedings of the National Academy of Sciences of the United States of America 99(22): 14126-14131, 2002

Abeta immmunization of PSAPP mice leads to decreased cerebral Abeta and a corresponding increase in serum Abeta. Society for Neuroscience Abstracts 27(2): 1807, 2001

Preparation, physiochemical characterization, and oral immunogenicity of Abeta(1-12), Abeta(29-40), and Abeta(1-42) loaded PLG microparticles formulations. Journal of Pharmaceutical Sciences 98(6): 2027-2039, 2008

Quantifying amyloid beta-peptide (Abeta) aggregation using the Congo red-Abeta (CR-abeta) spectrophotometric assay. Analytical Biochemistry 266(1): 66-76, 1999

Amyloid beta -protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways. Proceedings of the National Academy of Sciences of the United States of America 100(1): 330-335, 2002

Single chain variable fragments against beta-amyloid (Abeta) can inhibit Abeta aggregation and prevent abeta-induced neurotoxicity. Biochemistry 43(22): 6959-6967, 2004

The arctic mutation in the Abeta region of APP causes Alzheimers disease with increased Abeta protofibril formation and decreased Abeta peptide levels. Society for Neuroscience Abstracts 26(1-2): Abstract No -587 8, 2000

Angiotensin-converting enzyme converts amyloid beta-protein 1-42 (Abeta(1-42)) to Abeta(1-40), and its inhibition enhances brain Abeta deposition. Journal of Neuroscience 27(32): 8628-8635, 2007